Protein tyrosine kinases (PTKs) are enzymes which catalyse the phosphorylation of specific tyrosine residues in protein. The post-translational modification of these substrate proteins, often enzymes themselves, acts as a molecular switch regulating cell proliferation and activation. Abnormal PTK activity has been observed in many disease states including benign and malignant proliferative disorders as well as diseases resulting from inappropriate activation of the immune system (autoimmunity, allograft rejection and graft versus host disease). It is believed that compounds which selectively inhibit the responsible PTKs may be useful therapeutic agents.
Compounds of formula A ##STR3## in which R.sub.1 is aryl, R.sub.2 is hydrogen, lower alkyl or halo and R.sub.3 is aryl are disclosed as inhibitors of the protein tyrosine kinase pp60.sup.c-src in WO96/10028. Compounds of formula A in which R.sub.1 is unsubstituted or substituted cyclo-lower alkyl or cyclo-lower alkenyl and R.sub.2 and R.sub.3 are as previously defined are disclosed in co-pending application WO 97/28161. Compounds of formula A in which R.sub.1 is lower alkyl or substituted lower alkyl and R.sub.2 and R.sub.3 are as previously defined are disclosed in co-pending application WO 97/32879.
Compounds of formula B ##STR4## wherein X is --N or CR.sub.7, where R.sub.7 is hydrogen, halogen, loweralkyl, loweralkoxy or -S-loweralkyl; Y is --N or --CH; R.sub.1 and R.sub.2 are each independently hydrogen, hydroxy, alkoxy, or acyloxy or R.sub.1 and R.sub.2 are both hydroxy protected with an individual hydroxy protecting group or with a single dihydroxy-protecting group or R.sub.1 and R.sub.2 are absent and there is a double bond between the carbon atoms to which R.sub.1 and R.sub.2 are attached; R.sub.3 is hydrogen, hydroxy, loweralkyl or alkoxy; R.sub.4 is inter alia (a) hydrogen, (b) amino, (c) halogen, (d) hydroxy or R.sub.3 and R.sub.4 taken together are .dbd.O, or taken together with the carbon atom to which they are attached, form a spirocyclic ring; R.sub.5 is inter alia hydrogen, loweralkyl or amino; and R.sub.6 is inter alia loweralkyl, aryl, heteroaryl or heteroarylalkyl; are disclosed as being adenosine kinase inhibitors in WO 96/40686.